title: Selection of putative colorectal cancer markers by applying PCA on the soluble proteome of tumors: NDK A as a promising candidate.
abstract: Aiming to find new tumor markers for colorectal cancer (CRC), we applied proteomic methodologies to compare the soluble sub-proteome of healthy and tumoral colorectal mucosa. Out of 91 differentially expressed proteins, 23 were selected by principal component analysis (PCA) as the major contributors to the overall difference detected. After MS/MS analysis, 16 proteins were identified. From those, we chose 14-3-3-zeta/delta, retinoblastoma-binding protein 4 (RBBP-4), DJ-1, and nucleoside diphosphate kinase A (NDK A) for further studies, on the basis of their levels and known implication in cancer. Specific immunodetection demonstrated only the NDK A levels allowed to differentiate healthy mucosa from tumor tissue in all the patients. Hence, we used the colon cancer cell line Caco-2 to study the relationship between NDK A and colon cell tumorigenesis, finding it over-expressed in undifferentiated (tumor-like) cells regarding the differentiated ones. Noticeably, we also found increased levels of the NDK A in the secretome of tumor-like cells and, as expected, indications of higher levels of NDK A in the serum of CRC patients. In conclusion, the four validated proteins could constitute a panel of tissue markers for CRC, being the NDK A the most interesting candidate for further serum biomarker studies.
authors.affiliation: Departamento de Bioquímica, Genética e Inmunología, Facultad de Biología, Universidad de Vigo, Campus Universitario, 36310 Vigo, Spain.
authors.forename: Paula
authors.initials: P
authors.lastname: Alvarez-Chaver
authors.forename: Ana M
authors.initials: AM
authors.lastname: Rodríguez-Piñeiro
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Rodríguez-Berrocal
authors.forename: Andrés
authors.initials: A
authors.lastname: García-Lorenzo
authors.forename: María
authors.initials: M
authors.lastname: Páez de la Cadena
authors.forename: Vicenta S
authors.initials: VS
authors.lastname: Martínez-Zorzano
mesh_terms: D048948:14-3-3 Proteins / Q000032:analysis; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D018938:Caco-2 Cells; D015179:Colorectal Neoplasms / Q000175:diagnosis*; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000737:chemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis; D008297:Male; D008875:Middle Aged; D054778:NM23 Nucleoside Diphosphate Kinases / Q000032:analysis*; D015513:Oncogene Proteins / Q000032:analysis; D025341:Principal Component Analysis; D000071617:Protein Deglycase DJ-1; D020543:Proteome / Q000032:analysis; D056505:Retinoblastoma-Binding Protein 4 / Q000032:analysis; D053719:Tandem Mass Spectrometry
chemical_list: D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D015513:Oncogene Proteins; D020543:Proteome; D056505:Retinoblastoma-Binding Protein 4; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1